We propose to evaluate the feasibility of expressing human cytochrome P450 (CYP) cDNAs in Caco-2 human intestinal epithelial cells, a model system for the study of drug/xenobiotic uptake and transport. Expression studies will be conducted using CYP2A6 as a convenient and appropriate model enzyme and then extended to CYP3A4, the major cytochrome P450 in human intestinal epithelium. The suitability of transfected cells for studies of xenobiotic transport will also be evaluated. The overall goal is to develop Caco-2 cell derivatives which express the human cytochrome P450s found in the intestine in vivo in order to establish a better in vitro model system for drug transport / metabolism and for detecting the potential therapeutically relevant drug-drug or drug-nutrient interactions. PROPOSED COMMERCIAL APPLICATION: An improved in vitro model system to study drug metabolism and uptake. A useful system to help choose which drug candidates should be developed.